Although the synaptic organization and physiological responses of retinal neurons are fairly well understood, the transmitters used by most of these neurons are yet to be identified. In particular, the neurotransmitters used by photoreceptor, bipolar and ganglion cells remain unknown. A direct approach to this problem is to localize neurotransmitters using homogeneous populations of these cell types. Here, we propose novel methods for obtaining such cell preparations by tagging specific retinal neurons with fluorescent markers and separating the labeled from unlabeled cells using a Fluorescence Activated Cell Sorter. For this purpose, ganglion cells will be labeled by retrograde axonal transport of Lucifer Yellow injected into the optic chiasm. The bipolar cells will be labeled with Lucifer Yellow by incubation in the absence of Ca2 ions. The labeled cells will be dispersed by papain treatment and mechanical dissociation of retinas and separated by the cell sorter. Isolated photoreceptors tagged with FITC-antiopsin will also be separated in a similar manner. A second method is to react dissociated cells with antiopsin-coated magnetic spheres and separate the bound photoreceptors by magnetophoresis. The isolated ganglion, bipolar and photoreceptors cells will be used to study the biosynthesis, uptake, release and metabolism of transmitter candidates. These cells will also be used to characterize transmitter receptors and surface antigens. The localization, development and degeneration of cholinergic, GABAergic, dopaminergic, glycinergic and peptidergic neurons will be examined in normal and dystrophic retinas using neurotransmitters as biochemical probes.